ZC3H13 Promotes NSUN4-Mediated Chondrocyte Mitochondrial Dysfunction and Pyroptosis in Temporomandibular Joint Osteoarthritis.

Abstract

ObjectiveTemporomandibular joint osteoarthritis (TMJOA) seriously influences the quality of life of patients. Chondrocyte mitochondrial dysfunction and pyroptosis play an important role in the development of osteoarthritis, but their role in TMJOA pathogenesis is elusive. We aimed to probe into the role and mechanism of mitochondrial dysfunction and pyroptosis in TMJOA.DesignTMJOA rat models were established by unilateral anterior crossbite operation. Pathological changes in cartilage tissues were observed by hematoxylin-eosin staining, and mitochondrial dysfunction and pyroptosis were evaluated by immunohistochemistry. The biological function and mechanism of ZC3H13 in mitochondrial dysfunction and pyroptosis were determined by cell experiments.ResultsWe discovered that mitochondrial dysfunction and pyroptosis occurred in cartilage tissues of TMJOA rats. The expression of ZC3H13 was observably upregulated in TMJOA rats. Further cell experiments showed that interference of ZC3H13 restrained mitochondrial dysfunction and pyroptosis of chondrocytes. RNA sequencing revealed that NSUN4 expression was significantly increased in chondrocytes after ZC3H13 knockdown. Silencing of ZC3H13 remarkably diminished the level of NSUN4 N6-methyladenosine (m6A) modification. Moreover, mitochondrial dysfunction and pyroptosis of chondrocytes were notably increased after NSUN4 knockdown.ConclusionOur study revealed that ZC3H13-mediated NSUN4 repressed TMJOA progression by modulating chondrocyte mitochondrial dysfunction and pyroptosis in an m6A-dependent manner, which may offer a potential strategy for TMJOA treatment.